Survival in Branching Cellular Populations

TL;DR

This paper models the evolutionary dynamics in branching cellular populations, revealing how geometry influences strain survival and identifying an optimal branching rate for neutral strains.

Contribution

It introduces a statistical model capturing how branching geometry affects evolutionary survival, highlighting the role of inflation and branch termination.

Findings

Branch bifurcations increase survival probability due to population growth.

Small branch tips raise extinction risk for strains.

An optimal branching rate maximizes neutral strain survival.

Abstract

We analyze evolutionary dynamics in a confluent, branching cellular population, such as in a growing duct, vasculature, or in a branching microbial colony. We focus on the coarse-grained features of the evolution and build a statistical model that captures the essential features of the dynamics. Using simulations and analytic approaches, we show that the survival probability of strains within the growing population is sensitive to the branching geometry: Branch bifurcations enhance survival probability due to an overall population growth (i.e., "inflation"), while branch termination and the small effective population size at the growing branch tips increase the probability of strain extinction. We show that the evolutionary dynamics may be captured on a wide range of branch geometries parameterized just by the branch diameter $N_0$ and branching rate $b$. We find that the survival probability of neutral cell strains is largest at an "optimal" branching rate, which balances the effects of inflation and branch termination. We find that increasing the selective advantage $s$ of the cell strain mitigates the inflationary effect by decreasing the average time at which the mutant cell fate is determined. For sufficiently large selective advantages, the survival probability of the advantageous mutant decreases monotonically with the branching rate.